Identification of the immune gene expression signature associated with recurrence of high-grade gliomas

Roura, Adria‐Jaume; Gielniewski, Bartłomiej; Pilanc, Paulina; Szadkowska, Paulina; Maleszewska, Marta; Król, Sylwia; Czepko, Ryszard; Kaspera, Wojciech; Wojtaś, Bartosz; Kamińska, Bożena

doi:10.1007/s00109-020-02005-7

Cited by 11 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, the increased proportion of M2‐like TAMs in recurrent malignant gliomas compared to primary malignant gliomas was specific and consistent (Figure 2F ). The result is consistent with previous studies: the proportion of M2 TAMs in recurrent malignant glioma is significantly higher than that in primary malignant glioma, 39 , 40 which greatly impedes the treatment of malignant glioma. However, the exact mechanism remains unclear.…”

Section: Resultssupporting

confidence: 93%

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

et al. 2023

View full text Add to dashboard Cite

AimsTumor‐associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2‐like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.MethodsWe employed single‐cell RNA sequencing to construct a single‐cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.ResultsSix subgroups of TAMs were annotated and M2‐like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up‐regulation of several cancer pathways and intercellular interaction‐related genes are associated with the recurrence of malignant glioma. Moreover, the M2‐like TAMs can activate the PI3K/Akt/HIF‐1α/CA9 pathway in the malignant glioma cells via SPP1‐CD44‐mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.ConclusionOur study uncovers the distinction of M2‐like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.

show abstract

Section: Resultssupporting

confidence: 93%

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

et al. 2023

View full text Add to dashboard Cite

show abstract

“…First, we performed targeted sequencing to identify somatic and germline variants in the tDNA and gDNA samples. The most frequently found somatic mutations in the cohort were PTEN , TP53 , EGFR , ATRX , IDH1 , and NF1 ( Figure 5 A), in coherence with the findings in our previous study [ 43 ]. We used an oncodriveCLUST algorithm [ 44 ] to identify cancer drivers based on mutational clustering and found several variants enriched at the TP53 (five clusters), RECQL4 (one cluster), PIK3CA (two clusters), and IDH1 (one cluster) genes, among many others ( Figure 5 B).…”

Section: Resultssupporting

confidence: 90%

Improvements in Quality Control and Library Preparation for Targeted Sequencing Allowed Detection of Potentially Pathogenic Alterations in Circulating Cell-Free DNA Derived from Plasma of Brain Tumor Patients

Szadkowska

Roura

Wojtaś

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Malignant gliomas are the most frequent primary brain tumors in adults. They are genetically heterogenous and invariably recur due to incomplete surgery and therapy resistance. Circulating tumor DNA (ctDNA) is a component of circulating cell-free DNA (ccfDNA) and represents genetic material that originates from the primary tumor or metastasis. Brain tumors are frequently located in the eloquent brain regions, which makes biopsy difficult or impossible due to severe postoperative complications. The analysis of ccfDNA from a patient’s blood presents a plausible and noninvasive alternative. In this study, freshly frozen tumors and corresponding blood samples were collected from 84 brain tumor patients and analyzed by targeted next-generation sequencing (NGS). The cohort included 80 glioma patients, 2 metastatic cancer patients, and 2 primary CNS lymphoma (PCNSL) patients. We compared the pattern of genetic alterations in the tumor DNA (tDNA) with that of ccfDNA. The implemented technical improvements in quality control and library preparation allowed for the detection of ctDNA in 8 out of 84 patients, including 5 out of 80 glioma patients. In 32 out of 84 patients, we found potentially pathogenic genetic alterations in ccfDNA that were not detectable in tDNA. While sequencing ccfDNA from plasma has a low efficacy as a diagnostic tool for glioma patients, we concluded that further improvements in sample processing and library preparation can make liquid biopsy a valuable diagnostic tool for glioma patients.

show abstract

“…The co-existence of several cell sub-populations enhances the heterogeneity with diverse genetic, transcriptional, and functional backgrounds within the bulk tumor. 86 , 87 , 88 , 89 Prominent among these sub-populations are glioblastoma stem-like cells (GSCs), a subset of undifferentiated cells capable of self-renewal and multi-lineage differentiation. They are considered tumor-initiating cells that render cancer resistant to conventional anti-glioblastoma therapies, 90 , 91 , 92 , 93 leading to inevitable recurrence and fatal outcomes.…”

Section: Mir-128-3p In Malignancies Of the Cnsmentioning

confidence: 99%

MiR-128-3p – a gray eminence of the human central nervous system

Kiel,

Król,

Bronisz

et al. 2024

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Identification of the immune gene expression signature associated with recurrence of high-grade gliomas

Cited by 11 publications

References 45 publications

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

Improvements in Quality Control and Library Preparation for Targeted Sequencing Allowed Detection of Potentially Pathogenic Alterations in Circulating Cell-Free DNA Derived from Plasma of Brain Tumor Patients

MiR-128-3p – a gray eminence of the human central nervous system

Contact Info

Product

Resources

About